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Biomedical subjects

K C Anderson

Publications and source records attributed to K C Anderson.

At least 145 records · Page 8Linked to original sources
PubMed1995

Activation of pp90rsk and early growth response-1 gene expression by pokeweed mitogen in human B cells.

The present studies have examined the effects of pokeweed mitogen (PWM) on the induction of early growth response-1 gene (EGR-1) in normal human B cells. PWM regulates EGR-1 gene expression by both transcriptional and post-transcriptional mechanisms. Transient transfection assays with EGR-1 promoter fragments linked to the chloramphenicol acetyltransferase (CAT) gene demonstrated that PWM induced EGR-1 transcription is conferred by the CArG motif (C C[AT]6GG) in the EGR-1 promoter. The results further demonstrated the activation of S6 kinase (pp90rsk), evidenced by phosphorylation of S6 and serum response factor (SRF) peptides, in PWM treated B cells. Taken together, these findings suggest that PWM is able to initiate an intracytoplasmic signalling cascade and EGR-1 induction in normal human B cells.

Amino Acid Sequence↗
PubMed1995

Recombinant growth factors.

Recombinant human growth factors are expected to have a significant impact on the use of allogeneic blood components. For example, subsequent to the approval of recombinant human erythropoietin, blood transfusions in renal dialysis patients declined substantially. Likewise, myeloid growth factors have reduced infections and hospital stay by promoting hematologic recovery after high dose ablative chemotherapy. The high costs of these agents mandate that their use be limited to settings where they are clinically indicated. The use of growth factors may be monitored at medical centers by hospital transfusion committees. This chapter reviews the emerging clinical guidelines for the use of hematopoietic growth factors.

Adult↗
PubMed1995

A comparison of peripheral blood stem cell apheresis using the Fenwal CS3000 Plus and COBE Spectra.

We have compared the leukapheresis products collected on the Fenwal CS3000 Plus and COBE Spectra in a well-controlled patient population. While statistically significant differences were found, i.e. in product hematocrit, volume, number of granulocytes and platelets collected, these are not felt to be physiologically important. Similar efficiency in collecting mononuclear cells and colony forming unit assay results indicate that each instrument is capable of harvesting hematopoietic progenitor cells from peripheral blood.

Adult↗
PubMed1995

Characterization of reactions after exclusive transfusion of white cell-reduced cellular blood components.

BACKGROUND: Potential adverse effects of white cells (WBCs) within transfused cellular blood components include febrile nonhemolytic transfusion reactions (FNHTRs), alloimmunization, transmission of infectious diseases, transfusion-related acute lung injury, and immunomodulation. Although exclusive use of WBC-reduced components to prevent alloimmunization and cytomegalovirus transmission has been studied, the use of these components to avert FNHTR has not been examined. STUDY DESIGN AND METHODS: Transfusion reactions (FNHTRs, allergic reactions, and others) were characterized in recipients of 12,277 WBC-reduced single-donor apheresis platelets (SDAPs) and/or red cells (RBCs). Medical and laboratory evaluations for possible infectious and immunologic (alloimmunization) causes of each reaction were undertaken, and the benefit of further modification of components for the prevention of subsequent reactions was also evaluated. RESULTS: Transfusion reactions occurred after 481 (3.92%) of 12,277 transfusions. Allergic reactions occurred more commonly after transfusion of SDAPs (3.69%) than of RBCs (0.51%). Conversely, FNHTRs occurred more commonly after transfusion of RBCs (2.15%) than of SDAPs (1.58%). HLA antibodies were present in a posttransfusion sample from 27 (10.6%) of 255 patients; bacterial contamination was a possible cause of only 2 (0.42%) of 481 reactions. In patients with recurrent FNHTRs, further WBC reduction in components did not wholly prevent further FNHTRs. CONCLUSION: The incidence of FNHTRs and alloimmunization after exclusive transfusion of WBC-reduced RBCs and SDAPs was low. Further WBC reduction in components transfused to patients with a history of recurrent FNHTRs does not completely prevent subsequent reactions.

Antibodies↗
PubMed1995

Transfusion practices in human immunodeficiency virus-infected patients.

BACKGROUND: The reported immunomodulatory effects of transfusion raise concern about the potential for virus activation and tumor growth in human immunodeficiency virus (HIV)-infected patients. In the absence of "standards" of transfusion practice for such patients, a survey of transfusion policies among institutions specializing in the care of HIV-infected patients was performed to delineate current practices. STUDY DESIGN AND METHODS: A survey developed by the Transfusion Practices Committee of the American Association of Blood Banks was sent to 47 AIDS clinical trial units and 14 regional hemophilia centers in North America. RESULTS: Forty-three percent of centers completed the survey. Most centers observed more than 200 HIV-infected patients each. The key findings were that 1) 81 percent of centers used identical red cell transfusion criteria for HIV-infected and noninfected patients; 2) 52 percent used recombinant human erythropoietin as initial treatment for zidovudine-induced anemia, while 46 percent used recombinant human erythropoietin for anemia not associated with zidovudine; 3) 35 percent of centers used white cell-reduced blood components in lieu of cytomegalovirus (CMV)-seronegative components when administering transfusion(s) to CMV-seronegative patients; 4) 27 percent gamma-radiated cellular components, but no case of graft-versus-host disease had been observed; 5) > 85 percent of centers used monoclonal factor VIII for pediatric and adult hemophiliacs infected with HIV; 6) approximately one-third of centers routinely white cell-reduced cellular components; and 7) the most common reasons for white cell reduction included reduction of febrile reactions and CMV risk, reduction of platelet alloimmunization, and delay of immunomodulatory consequences of transfusion. CONCLUSION: There is marked heterogeneity in transfusion practice for HIV-infected patients. Modification of cellular components to achieve different objectives is routine in many centers.

Blood Transfusion↗
PubMed1995

Regulation of interleukin 6 in multiple myeloma and bone marrow stromal cells.

We and others have shown that some freshly isolated multiple myeloma (MM) cells and derived cell lines express interleukin 6 (IL-6) receptors and proliferate in vitro in response to IL-6; a subset of MM cells also expresses IL-6 mRNA, is intracytoplasmic IL-6 positive and secretes IL-6. We have shown that MM cells express the cell surface adhesion molecules CD29/CDw49d(VLA-4), CD18/CD11a(LFA-1) and CD44, and may localize to marrow via specific adherence to both extracellular matrix proteins and to bone marrow stromal cells (BMSCs). MM cell adhesion triggers IL-6 secretion by normal and MM BMSCs and related IL-6-mediated tumor cell growth. Our attempts to block MM cell adhesion to BMSC-induced IL-6 secretion by using antibodies to CD29/CDw49d, CD18/11a, and/or CD44 demonstrated minimal effects, suggesting that another ligand-receptor interaction triggers IL-6 secretion when MM cells and BMSCs are juxtaposed. Both MM cells and BMSCs express CD40. Triggering of MM cells and BMSCs via CD40 upregulates IL-6 secretion in both MM cells and MM-derived cell lines, as well as BMSCs and BMSC lines, suggesting the possibility of both autocrine and paracrine MM cell growth triggered via CD40. Finally, experiments using the LP 101 BMSC line transiently transfected with IL-6 promoter fragments linked to chloramphenicol acetyltransferase reporter gene demonstrate that adhesion of MM cells induces IL-6 gene transcription in BMSCs, which is conferred via the NF-kappa B binding motif.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Marrow↗
PubMed1994

Anti-CD38-blocked ricin: an immunotoxin for the treatment of multiple myeloma.

We report the development of a potent anti-CD38 immunotoxin capable of killing human myeloma and lymphoma cell lines. The immunotoxin is composed of an anti-CD38 antibody HB7 conjugated to a chemically modified ricin molecule wherein the binding sites of the B chain have been blocked by covalent attachment of affinity ligands (blocked ricin). Conjugation of blocked ricin to the HB7 antibody has minimal effect on the apparent affinity of the antibody and no effect on the ribosome-inactivating activity of the ricin A-chain moiety. Four to six logs of CD38+ tumor cell line kill was achieved at concentrations of HB7-blocked ricin in the range of 0.1 to 3 nmol/L. Low level of toxicity for normal bone marrow (BM) granulocyte-macrophage colony-forming units (CFU-GM), burst-forming units-erythroid (BFU-E), colony-forming units-granulocyte/erythroid/monocyte/macrophage (CFU-GEMM) cells was observed. Greater than two logs of CD38+ multiple myeloma cells were depleted from a 10-fold excess of normal BM mononuclear cells (BMMCs) after an exposure to HB7-blocked ricin under conditions (0.3 nmol/L) that were not very toxic for the normal BM precursors. HB7-blocked ricin was tested for its ability to inhibit protein synthesis in fresh patients' multiple myeloma cells and in normal BMMCs isolated from two healthy volunteers; tumor cells from four of five patients were 100-fold to 500-fold more sensitive to the inhibitory effect of HB7-blocked ricin than the normal BM cells. HB7 antibody does not activate normal resting peripheral blood lymphocytes, and HB7-blocked ricin is not cytotoxic toward these cells at concentrations of up to 1 nmol/L. The potent killing of antigen-bearing tumor cells coupled with a lack of effects on peripheral blood T cells or on hematopoietic progenitor cells suggests that HB7-blocked ricin may have clinical utility for the in vivo or in vitro purging of human multiple myeloma cells.

ADP-ribosyl Cyclase↗
PubMed1994

Identification of upstream signals regulating interleukin-6 gene expression during in vitro treatment of human B cells with pokeweed mitogen.

The present studies have characterized the regulation of interleukin-6 (IL-6) gene expression during pokeweed mitogen (PWM)-driven human B-cell differentiation. PWM induced an early and transient increase in the expression of immediate-early response genes of the jun/fos leucine zipper family (c-jun, jun B, c-fos, and fos-B). The induction of c-jun mRNA by PWM was concentration dependent. Nuclear run-on assays showed that PWM treatment is associated with an increased rate of c-jun gene transcription. The induction of c-jun mRNA precedes the induction of IL-6 gene expression and IL-6 secretion by the B cells. c-Jun antisense, but not sense, oligodeoxynucleotide (ODN) significantly decreases PWM-related B-cell (1) proliferation; (2) IL-6 mRNA induction; (3) IL-6 secretion; and (4) nuclear extract binding to AP-1 in electrophoretic mobility shift assay. In contrast, c-Fos anti-sense ODN did not effect either IL-6 mRNA induction or IL-6 secretion triggered in B cells by PWM. The results further show activation of c-Raf-1 kinase in PWM-treated B cells. Raf-1 acts upstream to mitogen-activated protein (MAP) kinase; therefore, studies were performed to assay for MAP kinase activation in these cells. The results show an increase in phosphorylation of myelin basic protein (MBP) and c-Jun "Y" peptide in PWM-treated B cells. Taken together, these findings suggest that PWM is able to initiate an intracytoplasmic signaling cascade in normal human splenic B cells, which, at least in part, involves serine/threonine protein kinases. These results show transient induction of immediate-early response genes in B cells and support a potential role for the c-jun gene product in regulation of IL-6 transcription and secretion.

B-Lymphocytes↗
PubMed1994

Involvement of serum response element in okadaic acid-induced EGR-1 transcription in human T-cells.

The present work has examined the effects of okadaic acid, an inhibitor of serine/threonine protein phosphatase, PP-1 and PP-2A, on the regulation of EGR-1 gene expression in normal peripheral blood T- and Jurkat cells. The results demonstrate that okadaic acid treatment is associated with a transient induction of EGR-1 gene expression which was detectable by 30 min to 1 h and peaked at 3-6 h. EGR-1 mRNA was superinduced in cells treated with both okadaic acid and the protein synthesis inhibitor cycloheximide. The half-life of EGR-1 mRNA was similar in both control and okadaic acid-treated cells. In contrast, treatment with both okadaic acid and cycloheximide prolonged the half-life of EGR-1 transcripts. Nuclear run-on assays demonstrated that induction of EGR-1 gene expression by okadaic acid is controlled at least in part by a transcriptional mechanism. Transient expression assays with EGR-1 promotor fragments linked to the chloramphenicol acetyltransferase gene demonstrate that okadaic acid-induced EGR-1 transcription is conferred by the 5' most distal CArG box, CC (AT)6GG, in the EGR-1 promoter. Moreover, chloramphenicol acetyltransferase activity was induced by okadaic acid when the 5' most distal CArG element was linked to the heterologous herpes simplex virus thymidine kinase promoter, and not induced with a similar heterologous construct containing a mutated CArG sequence. These studies demonstrate that okadaic acid regulates EGR-1 gene expression at the transcriptional level via the CArG element and suggest that PP-1 and PP-2A play a role in T-cell activation.

Base Sequence↗
PubMed1994

Guidelines for blood utilization review.

Hospitals are required by accrediting agencies to perform blood utilization review. Specific areas that must be addressed are the ordering, distribution, handling, dispensing, and administration of blood components. Monitoring the effects of transfusion on patients is also required. The format of the review process and the criteria for appropriate blood utilization must be developed by each institution. This article provides examples of areas that can be reviewed and procedures that may be used. However, the suggested laboratory values must not be interpreted as defining indications or criteria for transfusion. Each transfusion committee, or its equivalent, is responsible for developing its own institutional blood utilization procedures and audit criteria. Review and approval by the medical staff prior to implementation are essential. The procedures must also be reviewed and revised on a regular basis.

Blood Transfusion↗
PubMed1994

Multiple myeloma.

The mortality associated with multiple myeloma is due to the progressive accumulation of a clonal population of plasma cells in the bone marrow. Tumor cells may also be found in the blood and other extramedullary sites, especially in the terminal stages of the disease. During disease progression, numerous effects lead to significant morbidity, including immunosuppression, increased bone turnover, anemia, and renal deterioration. For more than two decades it has been realized that chemotherapy and radiotherapy could provide effective temporary relief from the pain and suffering associated with this malignancy. Unfortunately, these benefits are usually short lived, and essentially all patients experience recurrent disease that is usually refractory to additional therapy.

Chromosome Aberrations↗
PubMed1994

Cell surface expression and functional significance of adhesion molecules on human myeloma-derived cell lines.

Multiple myeloma is characterized by the presence of malignant plasma cells predominantly localized in bone marrow. Our prior studies have suggested that human myeloma derived-cell lines adhere specifically to fibronectin and to bone marrow stromal cells (BMSCs) via beta 1 and beta 2 integrins as well as RGD peptide, and that tumour cell to BMSC contact triggers interleukin-6 (IL-6) secretion from BMSCs. Since IL-6 is a growth factor for myeloma, adhesion may be important in paracrine IL-6 mediated tumour cell growth. We therefore examined phenotypic expression of adhesion molecules on the U266 and IM-9 human myeloma-derived cell lines using the panel of monoclonal antibodies (MoAbs) directed at adhesion molecules submitted to the Vth International Conference on Human Leukocyte Differentiation Antigens. U266 and IM-9 myeloma cell lines express mainly CD29, CD49d, VLA-1, CD18, CD54, ICAM-2 and ICAM-3. In contrast, CD49b, VLA-3, CD49f, CD11b, VCAM-1, selectins and selectin-ligands were not expressed on these cell lines. Specific adherence of IM-9 cells to BMSC line LP101 was demonstrated which could be partially blocked by pre-incubation and culture of tumour cells with anti-beta 1 integrin, anti-beta 2 integrin, anti-CD49d, anti-VLA-5, anti-CD11a, anti-CD44 and anti-CD54 MoAbs. The combination of these MoAbs (anti-CD29, CD18, CD11a, CD49d, VLA-5, CD44, CD54, ICAM-2, ICAM-3 MoAbs) decreased but did not completely abrogate binding of IM-9 to BMSCs. Moreover, increases in IL-6 secretion from BMSCs after adherence of IM-9 cells were also partially blocked by these MoAbs. These findings suggest that multiple adhesion pathways may mediate adherence of myeloma cell lines to BMSCs, localizing tumour cells in the marrow microenvironment and triggering IL-6 secretion by BMSCs which may augment tumour cell growth.

Antibodies, Monoclonal↗